Antihistamine and decongestants are used for the temporary relief of symptoms of the common cold, allergic rhinitis and sinusitis. The antihistaine brompheniramine and the decongestant pseudoephedrine are therapeutically indicated for patients needing relief of these symptoms.
Brompheniramine is a propylamine derivative antihistamine. Brompheniramine is a racemic mixture of the dextro and levo isomers. Pharmacologic activity is predominantly due to the d-isomer. Dextrobrompheniramine, the dextro isomer, is approximately twice as active. Brompheniramine is administered for its effects as a therapeutically acceptable salt, preferably as brompheniramine maleate. Brompheniramine maleate occurs as a white crystalline powder, freely soluble in aqueous-type fluids, and it is absorbed from the gastrointestinal tract.
Pseudoephedrine is a sympathomimetic drug which occurs naturally in plants of the Ephedra. Pseudoephedrine is a stereoisomer of ephedrine. Pseudoephedrine is administered for its beneficial effects as a therapeutically acceptable salt, preferably as the hydrochloride or the sulfate. Pseudoephedrine hydrochloride occurs as a fine, white crystal or powder; it is very soluble in aqueous-type fluids and it is absorbed from the gastrointestinal tract.
In copending patent application Ser. No. 06/839,384 a presentation is set forth concerning the desirability of providing a pharmaceutical dosage form comprising the two different drugs that are initially delivered in a therapeutically effective amount, followed by delivery of the drugs at a controlled rate, and for a time period, established to meet a specific therapeutic need. That is, as discussed therein, it would be desirable to provide a dosage form that comprises an exterior lamina comprising pseudoephedrine, brompheniramine and a releasable binder, which lamina delivers both drugs immediately for substantially eliminating the start-up time of the dosage form and for providing immediate therapy to a recipient. The exterior drug-containing lamina for delivering an initial drug-pulse act in cooperation with the dosage form that follows with the drugs then delivered at a controlled rate over time.
Additionally, as discussed therein, it would be desirable to provide a pharmaceutical dosage form comprising the two different drugs for their simultaneous administration for obtaining the physiological and the pharmacological benefits of each drug. Such a novel dosage form could be used for the desired medical relief where each individual drug addresses different symptoms of the particular medical situation. Prior to the invention disclosed and claimed in application Ser. No. 06/839,384 the co-administration of these drugs in a predetermined ratio did not appear feasible. For example, prior to that application pseudoephedrine and brompheniramine appeared to be kinetically incompatible in a pharmaceutical osmotically-controlled dosage form for their respective administrations within prescribed ratios because of their individual osmotic properties and their solubilities. Additionally, before the copending application, it was unobvious from their pharmacokinetic properties that pseudoephedrine and brompheniramine could be administered from a dosage form to a warm-blooded animal at rates that are individually selected to achieve each of their separate therapeutic plasma concentrations.
Thus, in the light of the above presentation, it will be appreciated by those skilled in the dispensing art that the novel and unique dosage form disclosed and claimed in the copending application Ser. No. 06/839,384 has made available (1) administering a pulsed amount of pseudoephedrine and brompheniramine and (2) made available a means for housing the pseudoephedrine and the brompheniramine for their administration at a controlled and continuous rate and in therapeutically effective ratio for obtaining the benefits of each drug, has a definite use and also represents a valuable contribution to the dispensing art. Also, it will be appreciated by those versed in the dispensing art that if an improvement is made available in the means for providing a pulsed amount of pseudoephedrine and brompheniramine from the dosage form, the improvement also will have a definite use and represent an additionally valuable contribution to the dispensing art.